Human Gene Module / Chromosome 1 / NUP133

NUP133nucleoporin 133kDa

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
5 / 0
Aliases
NUP133, hNUP133
Associated Syndromes
-
Chromosome Band
1q42.13
Associated Disorders
-
Relevance to Autism

Three de novo variants (two missense variants and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) have been identified in the NUP133 gene in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012; Iossifov et al., 2014). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 3.01E-03 (Takata et al., 2016).

Molecular Function

The protein encoded by this gene is a structural constituent of the nuclear pore and is involved in poly(A)+ RNA transport.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to NUP133 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Primary De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Recent Recommendation De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia Takata A , et al. (2016) No -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Isabelle Schrauwen et al. (2024) No -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.78C>G p.Gly26%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_gain Unknown - Simplex 38755281 Isabelle Schrauwen et al. (2024)
c.2146A>G p.Met716Val missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2694A>G p.Ser898= synonymous_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.386C>T p.Ala129Val missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Three de novo variants (two missense variants and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) have been identified in the NUP133 gene in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012; Iossifov et al., 2014). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 3.01E-03 (Takata et al., 2016).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Three de novo variants (two missense variants and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) have been identified in the NUP133 gene in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012; Iossifov et al., 2014). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 3.01E-03 (Takata et al., 2016).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Three de novo variants (two missense variants and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) have been identified in the NUP133 gene in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012; Iossifov et al., 2014). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 3.01E-03 (Takata et al., 2016).

Reports Added
[New Scoring Scheme]
4/1/2016
icon
4

Increased from to 4

Description

Three de novo variants (two missense variants and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) have been identified in the NUP133 gene in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012; Iossifov et al., 2014). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 3.01E-03 (Takata et al., 2016).

Krishnan Probability Score

Score 0.49502805117051

Ranking 3265/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.06623241961549

Ranking 8269/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94619412835936

Ranking 16772/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.43655816364522

Ranking 1069/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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